A Controlled Trial of Renal Denervation for Resistant Hypertension (SYMPLICITY-HTN-III)

Selected in The New England Journal of Medicine by G. Harris



Deepak L. Bhatt, David E. Kandzari, William W. O'Neill, Ralph D'Agostino, John M. Flack, Barry T. Katzen, Martin B. Leon, Minglei Liu, Laura Mauri, Manuela Negoita, Sidney A. Cohen, Suzanne Oparil, Krishna Rocha-Singh, Raymond R. Townsend, George L. Bakris


N Engl J Med 2014; 370:1393-1401


April 2014


Access the article here

My Comment


The SYMPLICITY HTN 1 & 2 trials generated a lot of excitement and momentum for the use of renal denervation (RD) in patients with resistant hypertension.

Renal artery denervation involves a radiofrequency ablative procedure of the sympathetic nerve endings in the renal arteries.

In the SYMPLICITY I trial (pilot study, Lancet 2009), this was a 38 minute median procedure involving 4 ablations per artery. This trial involved an original cohort of 45 patients @ 12 months, which was increased to 81 patients after 2 years. 31% of these patients were type 2 diabetics. 21% of the patients were on spironolactone. There was no significant change in renal function after 12 months.

The SYMPLICITY-HTN-2 trial was a randomized control trial involving 106 patients, randomized 1:1 renal denervation vs. control. The inclusion criteria, a systolic bp > 160mmHg, however type 2 diabetics with a systolic bp of > 150 mmHg were included. In this trial 84% of the patients in the RD group had a greater or equal than 10mmHg reduction in SBP, and 10 % of these patients had no reduction in systolic BP. 

The SYMPLICITY-HTN-3 trial enrolled 535 patients with a systolic blood pressure greater or equal to a 160mmHg (measured on 3 occasions, who were on at least 3 antihypertensive drugs (maximally tolerated dose, including a diuretic, to a 2:1 RD:sham procedure ratio.

Major findings

  • The change in the mean systolic blood pressure @ 6 months was -14.13+-23.93mmHg in the denervation group vs -11.74+-25mmHg in the sham procedure group (P < 0.001 for both). The difference -2.39mmHg (P=0.26 for superiority with a margin of 5mmHg).
  • The change in 24 hour ambulatory systolic blood pressure was -6.75+-15.11mmHg in the denervation group and -4.79 +-17.25mmHg in the sham procedure group (P= 0.98 for superiority with a margin of 2mmHg.
  • There was no difference in the incidence of serious adverse events.

My comment 

As pointed out in the editorial, spironolactone was used more than in the previous trials. There was also a considerable variability in the response to renal denervation, which begs the question as to uniformity of increased sympathetic drive contributing to the hypertension. Should the focus not shift to try and identify which patients fall in this group? 

For now I agree with Dr Valgimigli in that “renal denervation should be restricted to patients when they have tried at least 3 medications and still cannot reach their goal. And that it should not be offered to patients unless other available and proven therapies have systematically failed”.

This trial is very disappointing, and certainly has halted the current momentum in this direction, however it is premature to discount this form of therapy. Renal denervation, when it does work, creates an opportunity of avoiding amongst others the need for as many antihypertensive drugs with unwanted side effects. Especially given its relative safety and the hope of arriving at an otherwise unobtainable “safe” blood pressure.

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